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Koji Nitta,1 Yutaro Yamada,1 Satomi Morokado,1 Kazuhisa Sugiyama2 1Department of Ophthalmology, Fukui-Ken Saiseikai Hospital, Fukui, Fukui Prefecture, Japan; 2Department of Ophthalmology, Kanazawa University, Kanazawa, Ishikawa Prefecture, JapanCorrespondence: Koji NittaFukui-Ken Saiseikai Hospital, Funabashi 7-1, Wadanaka-Cho, Fukui City, Fukui 918-8503, JapanTel +81 776 23 1111Email nitta.koji7001@fukui.saiseikai.or.jpIntroduction: This study assesses two-year efficacy and safety following implantation of a single trabecular micro-bypass stent (iStent®) with concomitant phacoemulsification cataract surgery in Japanese patients with open-angle glaucoma (OAG).Materials and Methods: This retrospective, consecutive case series included eyes that underwent iStent implantation with phacoemulsification and were followed for 24 months postoperative. Efficacy and safety measures included intraocular pressure (IOP), number of glaucoma medications, adverse events, secondary surgeries, visual fields, and endothelial cell counts.Results: Of 73 operated eyes, 53 eyes had 24 months of follow-up and are analyzed. Diagnoses included primary open-angle glaucoma (POAG, n=25), normal-tension glaucoma (NTG, n=16), and pseudoexfoliative glaucoma (PXG, n=12). At 24 months, mean IOP reduced by 18% to 13.6± 3.0 mmHg versus 16.5± 3.4 mmHg preoperatively (p< 0.0001), and mean medication number reduced by 81% to 0.37± 0.74 versus 1.96± 0.98 preoperatively (p< 0.0001). The percentage of medication-free eyes was 77% versus 0% preoperatively, and 81% of eyes had IOP ≤ 15 mmHg versus 42% preoperatively. Results were similarly favorable across glaucoma subtypes (POAG, NTG, PXG). Notably, mean IOP in NTG eyes decreased to 12.8± 1.4 mmHg from 14.4± 3.0 mmHg preoperatively (p=0.03), and medications decreased by 87% to 0.31± 0.70 versus 2.38± 0.72 preoperatively (p< 0.0001). At 24 months, 81% of NTG eyes were medication-free (versus 0% preoperatively); 2 NTG eyes (13%) were on ≥ 2 medications (versus 100% preoperatively). Throughout the follow-up, visual fields and endothelial cell counts remained stable; 1 eye (1.9%) underwent filtration surgery.Discussion: Favorable safety and significant IOP and mediation reductions were achieved through two years following iStent implantation with phacoemulsification in a Japanese population. These gains were achieved across all glaucoma subtypes (including POAG, NTG, PXG).Conclusion: This real-world study supports the viability of iStent implantation to treat Japanese patients with glaucoma and shows that the benefits extend to those with NTG or PXG in addition to POAG.Keywords: microinvasive glaucoma surgery, MIGS, iStent, trabecular micro-bypass, Japanese, normal-tension glaucoma

Tsubasa Nishino, Akira Kobayashi, Natsuko Mori, Hideaki Yokogawa, Kazuhisa Sugiyama Department of Ophthalmology, Kanazawa University Graduate School of Medical Science, Kanazawa, JapanCorrespondence: Akira KobayashiDepartment of Ophthalmology, Kanazawa University Graduate School of Medical Science, 13-1 Takara-Machi, Kanazawa-shi, Ishikawa-ken 920-8641, JapanTel +81-76-265-2403Fax +81-76-222-9660Email eyekoba@gmail.comPurpose: To investigate in vivo corneal changes of genetically confirmed Reis–Bücklers corneal dystrophy (RBCD) and Thiel–Behnke corneal dystrophy (TBCD) using anterior segment optical coherence tomography (AS-OCT).Design: A single-center, prospective, comparative case series.Methods: Seven patients from 3 pedigrees (3 males, 4 females) with RBCD [Arg124Leu (R124L) heterozygous missense mutation of human transforming growth factor beta-induced (TGFBI) gene] and 4 patients from 3 pedigrees (3 males, 1 female) with TBCD [Arg555Gln (R555Q) heterozygous missense mutation of TGFBI gene] were examined. Six patients with RBCD and three patients with TBCD exhibited recurrence after corneal surgery including penetrating keratoplasty, phototherapeutic keratectomy, and electrolysis. All patients were examined by slit-lamp biomicroscopy followed by AS-OCT. Selected AS-OCT images of the cornea were evaluated qualitatively for changes in shape and degree of light reflection of corneal deposits.Results: Slit-lamp biomicroscopy showed characteristic irregular gray opacities in Bowman’s layer in each dystrophy: a geographic pattern in RBCD and a honeycomb pattern in TBCD. In each dystrophy, distinct characteristic deposits were observed by AS-OCT as a banding lesion in Bowman’s layer and its adjacent epithelium/stroma. In RBCD, the banding lesion was highly reflective and sharply margined at the stroma. In contrast, deposits in TBCD in the same layer showed a saw-tooth pattern toward the epithelium and poorly margined at the stroma.Conclusion: AS-OCT is able to clearly identify characteristic in vivo corneal microstructural changes associated with RBCD and TBCD. As a result, in vivo differentiation of RBCD and TBCD can be achieved.Keywords: Reis–Bücklers corneal dystrophy, Thiel–Behnke corneal dystrophy, anterior segment optical coherence tomography, genetic mutational analysis, human transforming growth factor beta-induced gene, TGFBI

Hideaki Yokogawa, Akira Kobayashi, Natsuko Mori, Tsubasa Nishino, Kazuhisa Sugiyama Department of Ophthalmology, Kanazawa University Graduate School of Medical Science, Kanazawa, JapanCorrespondence: Hideaki YokogawaDepartment of Ophthalmology, Kanazawa University Graduate School of Medical Science, 13-1 Takara-machi, Kanazawa-shi, Ishikawa-ken 920-8641, JapanTel +81-76-265-2403Fax +81-76-222-9660Email hyoko@med.kanazawa-u.ac.jpPurpose: To describe the visibility of the retina through an air-filled anterior chamber during simultaneous pars plana vitrectomy (PPV) and Descemet’s stripping automated endothelial keratoplasty (DSAEK), and to discuss the technical challenges of a fluid-air exchange under such conditions.Methods: Six eyes from 6 patients with coexisting bullous keratopathy and posterior segment problems such as vitreous opacity, retained silicon oil, intraocular lens subluxation, or aphakia underwent simultaneous PPV and DSAEK. In all cases, after completion of 25-gauge PPV with/without flanged intrascleral intraocular lens fixation, DSAEK donor tissue was inserted into the anterior chamber. Air was then injected into the anterior chamber to attach the donor graft to the back surface of the host cornea. At this point, the visibility of the retina was evaluated using endoillumination and a wide-angle viewing system.Results: In all cases, visibility of the retina through an air-filled anterior chamber, with the DSAEK donor attached, was sufficient to perform a fluid-air exchange.Conclusion: Our clinical observations of such rare but clinically important conditions indicate that simultaneous PPV and DSAEK is possible with fair visualization of the posterior segment including the retina.Keywords: Descemet’s stripping automated endothelial keratoplasty, pars plana vitrectomy

Koji Nitta,1,2 Gaku Tachibana,1,2 Ryotaro Wajima,1,2 Sachie Inoue,3 Tatsuya Ohigashi,4 Naomi Otsuka,4 Hiroaki Kurashima,4 Kazunori Santo,4 Masayo Hashimoto,4 Hidetoshi Shibahara,3 Mai Hirukawa,3 Kazuhisa Sugiyama2 1Department of Ophthalmology, Fukui-Ken Saiseikai Hospital, Fukui, Japan; 2Department of Ophthalmology, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan; 3CRECON Medical Assessment Inc., Tokyo, Japan; 4Japan Medical Affairs Group, Santen Pharmaceutical Co., Ltd., Osaka, JapanCorrespondence: Koji Nitta Email nitta.koji7001@fukui.saiseikai.or.jpPurpose: To maintain visual fields and quality of life over a lifetime, medical practice must be conducted taking into consideration not only visual field progression but also future visual field changes that occur over the patients’ expected lifespan. The purpose of this study is to investigate the feasibility of establishing a model that predicts prognosis, estimating the proportion of glaucoma patients with severe visual field defects.Patients and Methods: The data of 191 patients with primary open-angle glaucoma, with a predominance of normal-tension glaucoma, were used for this study. The model was developed based on patients’ backgrounds and risk factors, using Monte Carlo simulation. A “severe visual field defect” was defined as ≤-20 dB. The mean deviation (MD) value for 10,000 virtual patients in each simulation pattern (144 patterns) was calculated using a predictive formula to estimate the MD slope, and the effects of risk factors and intraocular pressure (IOP) reduction on the proportion of patients with severe visual field defects were evaluated.Results: Younger age, later-stage disease, more severe glaucomatous structural abnormalities and the presence of disc hemorrhage were associated with an increase in the progression rate of patients with severe visual field defects. Conversely, lower IOP was associated with a decrease in this rate.Conclusion: Combining regression analysis with Monte Carlo simulation could be a useful method for developing predictive models of prognosis in glaucoma patients.Keywords: glaucoma, epidemiology, prognosis, risk factors, simulation

Koji Nitta,1,2 Shiro Shimamoto,3 Ryotaro Wajima,2 Gaku Tachibana,2 Yutaro Yamada,1,2 Miyuki Domoto,1 Ryuji Takeda,4,5 Yoshinari Takahashi,6 Kazuhisa Sugiyama2 1Fukui-ken Saiseikai Hospital, Fukui, Japan; 2Department of Ophthalmology, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan; 3Shimamoto Ophthalmology Clinic, Fukui, Japan; 4Department of Nutritional Sciences for Well-Being, Faculty of Health Sciences for Welfare, Kansai University of Welfare Sciences, Osaka, Japan; 5Department of Applied Biological Chemistry, Faculty of Agriculture, Kindai University, Nara, Japan; 6Inary Co., Ltd., Tokyo, JapanCorrespondence: Koji NittaDepartment of Ophthalmology, Fukui-ken Saiseikai Hospital, 7-1 Funabashi, Wadanaka-cho, Fukui 918-8503, JapanTel +81 776 23 1111Fax +81 776 28 8515Email nitta.koji7001@fukui.saiseikai.or.jpBackground: This retrospective study evaluated the effect of adjunctive administration of brimonidine 0.1% on disc hemorrhage (DH) in patients with primary open-angle glaucoma or normal-tension glaucoma who were already treated with other anti-glaucoma drugs.Methods: Patients with DH, before adjunctive therapy with brimonidine, were enrolled. Subjects were excluded if their treatment regimen was changed within 1 year after initiation of adjunctive therapy with brimonidine. We investigated the frequency of DH and intraocular pressure (IOP). Both parameters were compared before and after adjunctive administration of brimonidine.Results: The frequency of DH before and after brimonidine administration was 0.67± 0.68 and 0.31± 0.72 times/year, respectively, with a significant decrease (P=0.01), and the mean IOP before and after brimonidine administration was 12.5± 1.9 and 11.2± 2.2 mmHg, respectively, (P=0.0006) with a significant reduction after adjunctive administration.Conclusion: The results of this study supported the hypothesis that the frequency of DH is reduced by brimonidine alongside lowering of IOP.Keywords: disc hemorrhage, intraocular pressure, brimonidine, primary open-angle glaucoma, normal-tension glaucoma

Tsubasa Nishino, Akira Kobayashi, Hideaki Yokogawa, Natsuko Mori, Kazuhisa SugiyamaDepartment of Ophthalmology, Kanazawa University Graduate School of Medical Science, Kanazawa, JapanPurpose: To present the changing indications and surgical techniques for keratoplasty during a 16-year period (2003–2018) at a tertiary referral hospital in Japan.Methods: Consecutive keratoplasty cases at Kanazawa University Hospital from January 2003 to December 2018 were retrospectively reviewed. Keratoplasty procedures included penetrating keratoplasty (PK), deep anterior lamellar keratoplasty (DALK), anterior lamellar keratoplasty (ALK), Descemet’s stripping automated endothelial keratoplasty (DSAEK), and Descemet’s membrane endothelial keratoplasty (DMEK). Annual numbers and types of keratoplasty as well as underlying diseases for PK and total keratoplasty procedures were recorded, and annual trends were statistically analyzed using Cochran–Armitage test for trend.Results: A total of 801 keratoplasty procedures (PK, 319 cases; DALK, 57 cases; ALK, 9 cases; DSAEK, 371 cases; and DMEK 45 cases; mean age, 66.9±16.3 years) were performed for 595 patients (302 males [329 eyes, 419 cases], 293 females [345 eyes, 382 cases]) during the 16-year period. The proportion of PK procedures decreased significantly in the beginning and showed a slightly increasing trend after a plateau around 2015. DSAEK was increasing after 2006 and reached a plateau around 2012. Among 10 underlying diseases for total keratoplasty, corneal opacity and dermoid were decreasing linearly. Failed PK and failed DSAEK were increasing linearly in the beginning and reached a plateau followed by a decreasing trend. In terms of the underlying disease for PK, bullous keratopathy was decreasing in the beginning and reached a plateau around 2015. A total of 19 PK procedures were performed on cases with recalcitrant bullous kerstopathy (BK) after 2010.Conclusion: The distribution of keratoplasty procedures and underlying diseases changed significantly over 16 years at a tertiary referral hospital in Japan. PK procedure was significantly decreased and DSAEK procedure was significantly increased. PK for BK decreased significantly; however, PK remains a viable option for other recalcitrant corneal diseases.Keywords: Descemet’s stripping automated endothelial keratoplasty, Descemet’s membrane endothelial keratoplasty, penetrating keratoplasty

Natsuko Mori,1,2 Hideaki Yokogawa,1 Akira Kobayashi,1 Tsubasa Nishino,1,3 Kazuhisa Sugiyama11Department of Ophthalmology, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan; 2Department of Ophthalmology, Saiseikai Kanazawa Hospital, Kanazawa, Japan; 3Department of Ophthalmology, Toyama Prefectural Central Hospital, Toyama, JapanPurpose: This study aimed to elucidate the frequency of surgery-induced iris abnormalities after Descemet membrane endothelial keratoplasty (DMEK) and their impact on postoperative clinical outcomes.Methods: In this retrospective study, medical records of 32 eyes from 28 consecutive patients (mean age, 65.7±13.4 years; 14 men, 18 women) who underwent DMEK (or triple DMEK) were reviewed. In all patients, inferior peripheral iridectomy was created leaving full intracameral air tamponade at the end of surgery. Sulfur hexafluoride gas was not used in any cases. Surgery-induced iris abnormalities such as pupillary shape changes and iris depigmentation were evaluated by 3 masked observers. Pre-existing abnormalities were excluded. Eyes were divided into two groups based on the presence of surgery-induced iris changes: Group A (with iris abnormalities) and Group B (without). Impacts on postoperative clinical outcomes such as vision and endothelial cell density were analyzed.Results: Surgery-induced iris abnormalities were seen in 15 eyes (Group A, 9 with pupillary shape change and 6 with iris depigmentation; 46.9%), and 17 eyes showed no abnormalities (Group B, 53.1%). No significant differences were detected between groups in age, sex, indication, simultaneous cataract surgery, pre- and 6-month postoperative vision, donor age, donor endothelial cell density, and 6- and 12-month postoperative endothelial cell density.Conclusions: Surgery-induced iris abnormalities were noted in almost half of the eyes after DMEK (46.9%) in this study. However, there was no association between visual outcomes or postoperative endothelial cell density and the iris changes.Keywords: surgery-induced iris abnormalities, DMEK

Tsubasa Nishino, Akira Kobayashi, Hideaki Yokogawa, Natsuko Mori, Toshinori Masaki, Kazuhisa Sugiyama Department of Ophthalmology, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan Purpose: To report a 10-year review of endothelial keratoplasty (EK) procedures, Descemet’s stripping automated endothelial keratoplasty (DSAEK) and Descemet’s membrane endothelial keratoplasty (DMEK), and underlying diseases at a tertiary referral hospital in Japan. Study design: A single-center, retrospective case series. Methods: We retrospectively reviewed all medical records of bullous keratopathy (BK) surgically treated by EK (DSAEK/DMEK) at Kanazawa University Hospital from January 2007 to December 2016. Changes or modifications to the annual number of EK procedures and underlying diseases were analyzed. Results: During this period, 320 EK procedures (DSAEK: 288 cases, DMEK: 32 cases) were performed on 250 patients. Total annual EKs gradually increased from 19 to 45 cases between 2007 and 2016. The annual number of DSAEKs was stable, although the proportion of DSAEKs to other procedures decreased significantly as re-DSAEKs and DMEKs increased. BK after argon laser iridotomy (ALI) was the leading cause in 2007, followed by Fuchs’ endothelial dystrophy (FED) and failed penetrating keratoplasty. In 2016, BK after trabeculectomy (TLE) was most prevalent, followed by failed DSAEK, failed penetrating keratoplasty, and pseudophakic BK. The decreased ALI and FED, and increased BK after TLE and failed DSAEK were statistically significant. Conclusion: The distribution of EK procedures (DSAEK/DMEK) and underlying diseases changed over 10 years at a tertiary referral hospital in Japan. The proportion of re-DSAEK and DMEK increased among all EK procedures. Most significantly, among the underlying diseases, decreased ALI and FED and increased TLE and failed DSAEK were observed. Extended multicenter analysis may further elucidate the changes in EK procedures and the causes of BK in Japan. Keywords: argon laser iridotomy, trabeculectomy, reoperation, Fuchs’ endothelial dystrophy

Daisuke Takemoto, Tomomi Higashide, Yoshiaki Saito, Shinji Ohkubo, Sachiko Udagawa, Hisashi Takeda, Kazuhisa Sugiyama Department of Ophthalmology, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan Purpose: We conducted a prospective study in patients with normal-tension glaucoma (NTG) who received either isopropyl unoprostone or latanoprost. We compared the drugs in terms of their effects on intraocular pressure (IOP) and visual field loss progression over a 3-year period. Study design: Prospective, randomized controlled study. Methods: We enrolled 48 patients with newly diagnosed NTG at Kanazawa University Hospital. Eligible patients were randomly allocated (1:1) to receive either unoprostone or latanoprost ophthalmic solutions. The primary outcomes were IOP changes and visual field deterioration within 36 months. Visual field changes were analyzed: the cumulative survival rates were calculated in terms of mean deviation, pattern standard deviation, and total deviation of the upper or lower hemi-visual field, each visual field sector, and guided progression analysis. In addition, we evaluated the progression of glaucomatous optic disc changes using fundus photography and confocal scanning laser ophthalmoscopy. Results: The mean pretreatment IOP was 15.0±2.4 mmHg in the Unoprostone group and 15.2±1.9 mmHg in the Latanoprost group. The mean IOP during the treatment period was 13.7±2.3 mmHg in the Unoprostone group and 13.0±1.8 mmHg in the Latanoprost group. In both groups, the IOP decreased significantly (p

Tsugihisa Sasaki,1 Tsutomu Sounou,2 Hideki Tsuji,3 Kazuhisa Sugiyama4 1Sasaki Eye Clinic, Mikuni, Sakai, 2Department of Ophthalmology, Keiju Kanazawa Hospital, 3Department of Ophthalmology, Cancer Institute Hospital, 4Department of Ophthalmology and Visual Science, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan Purpose: To facilitate the analysis of lacrimal conditions, we utilized high-definition dacryoendoscopy (HDD) and undertook observations with a pressure-controlled air-insufflation system. We report the safety and performance of HDD.Methods: In this retrospective, non-randomized clinical trial, 46 patients (14 males and 32 females; age range 39–91 years; mean age ± SD 70.3±12.0 years) who had lacrimal disorders were examined with HDD and conventional dacryoendoscopy (CD). The high-definition dacryoendoscope had 15,000 picture element image fibers and an advanced objective lens. Its outer diameter was 0.9–1.2 mm. Air insufflation was controlled at 0–20 kPa with a digital manometer-based pressure-controlled air-insufflation system to evaluate the quality of the image. The HDD had an air/saline irrigation channel between the outer sheath (outer diameter =1.2 mm) and the metal inner sheath of the endoscope. We used it and the CD in air, saline, and diluted milk saline with and without manual irrigation to quantitatively evaluate the effect of air pressure and saline irrigation on image quality.Results: In vivo, the most significant improvement in image quality was demonstrated with air-insufflated (5–15 kPa) HDD, as compared with saline-irrigated HDD and saline-irrigated CD. No emphysema or damage was noted under observation with HDD. In vitro, no significant difference was demonstrated between air-insufflated HDD and saline-irrigated HDD. In vitro, the image quality of air-insufflated HDD was significantly improved as compared with that of saline-irrigated CD.Conclusion: Pressure-controlled (5–15 kPa) air-insufflated HDD is safe, and yields significantly better image quality than CD and saline-irrigated HDD. Keywords: pressure-controlled air-insufflated, high-definition dacryoendoscopy, saline-irrigated dacryoendoscopy, emphysema

Akira Kobayashi, Hideaki Yokogawa, Natsuko Mori, Toshinori Masaki, Kazuhisa Sugiyama Department of Ophthalmology, Graduate School of Medical Science, Kanazawa University, Kanazawa, Japan Objective: To report the in vivo laser confocal microscopy findings of corneas with keratoconus, with special attention to abnormality of Bowman’s layer and sub-Bowman’s fibrous structures (Kobayashi-structures [K-structures]).Methods: Sixteen keratoconic eyes in 8 consecutive patients with keratoconus (4 males, 4 females, mean age, 41.1 years) were included in this study. Slit-lamp biomicroscopic photos were taken with or without fluorescein staining. The existence of anterior corneal mosaic (ACM) after eyelid rubbing under fluorescein staining was documented. In vivo laser confocal microscopic examinations were performed for all patients in both the central cone and the peripheral cornea to examine the existence of K-structures.Results: According to the Amsler–Krumeich scale, the eyes were graded as follows: stage 1 (n=3), stage 2 (n=1), stage 3 (n=1), and stage 4 (n=11). ACM was observed in 7 eyes (61.1%) in the cone area and 16 eyes (100%) in the peripheral cornea among all keratoconic eyes enrolled in this study. In addition, K-structures were observed in the 7 eyes (61.1%) and 16 eyes (100%) in the peripheral cornea among all keratoconic eyes. The presence of the K-structures was completely matched (100%) with the presence of ACM in both the central cone and the peripheral cornea. In 11 eyes with stage 4 keratoconus, ACM and K-structure was absent in 9 eyes (81.8%) in the cone area. On the contrary, in 5 eyes with mild-to-moderate keratoconus (grade 1 to 3), ACM and K-structure was present in all eyes (100%) in the cone area. The absent ratio of ACM and K-structures in the cone area was significantly higher in stage 4 severe keratoconus compared to mild-to-moderate keratoconus (grade 1 to 3) (Fisher, P=0.005).Conclusion: The existence of ACM and K-structures in both the central cone and the peripheral cornea showed perfect accord in patients with keratoconus, indicating a strong association of ACM and K-structures in patients with keratoconus. With the progress of the keratoconus, it seemed that ACM and K-structure progressively disappeared, suggesting Bowman’s layer abnormalities due to keratoconus. Further study in larger groups of patients with keratoconus is required to fully understand the significance of ACM/K-structures in keratoconic eyes and their association with Bowman’s layer. Keywords: keratoconus, anterior corneal mosaic, K-structure, confocal microscopy

Koji Nitta,1 Kazuhisa Sugiyama,2 Ryotaro Wajima,1 Gaku Tachibana1 1Department of Ophthalmology, Fukui-ken Saiseikai Hospital, Fukui, 2Department of Ophthalmology, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan Purpose: The purpose of this study was to clarify differences between highly myopic and non-myopic primary open-angle glaucoma (POAG) patients, including normal-tension glaucoma patients.Patients and methods: A total of 269 POAG patients were divided into two groups: patients with ≥26.5 mm of axial length (highly myopic group) and patients with

Hideaki Yokogawa, Akira Kobayashi, Natsuko Mori, Kazuhisa Sugiyama Department of Ophthalmology, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan Purpose: To produce a two-dimensional reconstruction map of dendritic lesions in patients with herpes simplex keratitis (HSK) using in vivo confocal microscopy.Methods: Four eyes of four patients (mean 65.8 years) with HSK presenting with a dendritic lesion were enrolled. Slit-lamp biomicroscopy and in vivo laser confocal microscopy were performed. Acquired confocal images at the level of the epithelium were arranged and mapped into subconfluent montages. Changes in the shape and degree of light reflection of abnormal cells and deposits around dendritic lesions as well as other corneal layers were qualitatively evaluated.Results: Mapping of dendritic lesion was successful in all cases, and the subconfluent montages clearly showed the larger image of dendritic lesion. In all cases, the dendritic lesion consisted of hyperreflective irregular epithelial cells, and was surrounded by distorted and elongated epithelial cells. In three cases, hyperreflective deposits were noted at the midline of the lesion. The corneal stroma showed a hyperreflective honeycomb pattern. In two cases, inflammatory cells were observed at the level of endothelial cell layer.Conclusion: Mapping of dendritic lesions in patients with HSK was successful in all patients using in vivo confocal microscopy. Cellular level observation of dendritic lesion at a relatively larger magnification may help understand the in vivo morphological change of HSK. Further study in more patients with HSK and nonherpetic dendritic lesion is needed to utilize confocal microscopy images in differential diagnosis and follow-up of the epithelial lesions with dendrite. Keywords: herpetic epithelial keratitis, in vivo confocal microscopy, fluorescein slit-lamp photograph, hyperreflective irregular epithelial cells, dendritic lesion

Hideaki Yokogawa, Akira Kobayashi, Natsuko Yamazaki, Toshinori Masaki, Kazuhisa Sugiyama Department of Ophthalmology, Kanazawa University Graduate School of Medical Science, Kanazawa, JapanPurpose: To report surgical therapies for corneal perforations in a tertiary referral hospital.Methods: Thirty-one eyes of 31 patients (aged 62.4±18.3 years) with surgically treated corneal perforations from January 2002 to July 2013 were included in this study. Demographic data such as cause of corneal perforation, surgical procedures, and visual outcomes were retrospectively analyzed.Results: The causes of corneal perforation (n=31) were divided into infectious (n=8, 26%) and noninfectious (n=23, 74%) categories. Infectious causes included fungal ulcer, herpetic stromal necrotizing keratitis, and bacterial ulcer. The causes of noninfectious keratopathy included corneal melting after removal of a metal foreign body, severe dry eye, lagophthalmos, canaliculitis, the oral anticancer drug S-1, keratoconus, rheumatoid arthritis, neurotrophic ulcer, atopic keratoconjunctivitis, and unknown causes. Initial surgical procedures included central large corneal graft (n=17), small corneal graft (n=7), and amniotic membrane transplantation (n=7). In two cases the perforation could not be sealed during the first surgical treatment and required subsequent procedures. All infectious keratitis required central large penetrating keratoplasty to obtain anatomical cure. In contrast, several surgical options were used for the treatment of noninfectious keratitis. After surgical treatment, anatomical cure was obtained in all cases. Mean postoperative best corrected visual acuity was better at 6 months (logMAR 1.3) than preoperatively (logMAR 1.8).Conclusion: Surgical therapies for corneal perforations in our hospital included central large lamellar/penetrating keratoplasty, small peripheral patch graft, and amniotic membrane transplantation. All treatments were effective. Corneal perforation due to the oral anticancer drug S-1 is newly reported. Keywords: corneal perforation, keratoplasty, amniotic membrane transplantation

Akira Kobayashi, Hideaki Yokogawa, Natsuko Yamazaki, Toshinori Masaki, Kazuhisa Sugiyama Department of Ophthalmology, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan Abstract: Here we report a case of endothelial keratoplasty with infant donor tissue obtained after brain death. A 52-year-old man with endothelial dysfunction of unknown cause in the right eye underwent non-Descemet stripping automated endothelial keratoplasty (nDSAEK) with tissue from an infant donor (2 years). Intraoperative and postoperative complications were recorded. Best corrected visual acuity and donor central endothelial cell density were recorded preoperatively and postoperatively. Infant donor tissue preparation with a microkeratome set at 300 µm was successful; the donor tissue was extremely elastic and soft compared with adult tissue. The central endothelial cell density of the infant donor tissue was as high as 4,291 cells/mm2. No complications were observed during donor tissue (8.0 mm in diameter) insertion with the double-glide technique (Busin glide with intraocular lens sheet glide) or any of the other procedures. Best corrected visual acuity improved from 1.7 logMAR (logarithm of the minimum angle of resolution; 0.02 decimal visual acuity) preoperatively to 0.2 logMAR (0.6) after 6 months and 0.1 logMAR (0.8) after 1 year. The central endothelial cell density after 6 months was 4,098 cells/mm2 (representing a 4.5% cell loss from preoperative donor cell measurements), and the central endothelial cell density after 1 year was 4,032 cells/mm2 (6.0% decrease). Infant donor tissue may be preferably used for DSAEK/nDASEK, since it may not be suitable for penetrating keratoplasty or Descemet membrane endothelial keratoplasty. Keywords: brain death, non-Descemet stripping automated endothelial keratoplasty, infant donor, endothelial keratoplasty

Akira Kobayashi, Tomomi Higashide, Hideaki Yokogawa, Natsuko Yamazaki, Toshinori Masaki, Kazuhisa Sugiyama Department of Ophthalmology, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan Objective: To report the in vivo laser confocal microscopy findings of a cornea with osteogenesis imperfecta (OI) with special attention to the abnormality of Bowman's layer and sub-Bowman's fibrous structures (K-structures). Patients and methods: Two patients (67-year-old male and his 26-year-old son) with OI type I were included in this study. Slit lamp biomicroscopic and in vivo laser confocal microscopic examinations were performed for both patients. Central corneal thickness and central endothelial cell density were also measured. Results: Although the corneas looked clear with normal endothelial density for both eyes in both patients, they were quite thin (386 µm oculus dexter (OD) (the right eye) and 384 µm oculus sinister (OS) (the left eye) in the father and 430 µm OD and 425 µm OS in the son). In both patients, slit lamp biomicroscopic and in vivo laser confocal microscopic examination showed similar results. Anterior corneal mosaics produced by rubbing the eyelid under fluorescein were completely absent in both eyes. In vivo laser confocal microscopy revealed an absent or atrophic Bowman's layer; a trace of a presumed Bowman's layer and/or basement membrane was barely visible with high intensity. Additionally, K-structures were completely absent in both eyes. Conclusion: The absence of K-structures and fluorescein anterior corneal mosaics strongly suggested an abnormality of Bowman's layer in these OI patients. Keywords: osteogenesis imperfecta, K-structure, confocal microscopy, Bowman's layer

Akira Kobayashi, Hideaki Yokogawa, Natsuko Yamazaki, Toshinori Masaki, Kazuhisa Sugiyama Department of Ophthalmology, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan Purpose: To report the first case of Descemet membrane endothelial keratoplasty (DMEK) for bullous keratopathy (BK) secondary to argon laser iridotomy (ALI).Patient: A 71-year-old woman presented with decreased visual acuity in her right eye due to BK secondary to ALI that was performed 10 years prior.Results: Phacosurgery was performed first, followed by successful DMEK 4 months later. A DMEK shooter was used for donor insertion, which allowed for a stable anterior chamber during donor insertion, even when the anterior chamber was quite shallow. Also, removal of edematous epithelial cells and endoillumination probe-assisted DMEK was quite useful to visualize DMEK graft on the background of the dark brown iris seen in Asian eyes. The patient’s best corrected visual acuity rapidly increased from 20/200 to 25/20 after 1 month, with complete resolution of corneal edema.Conclusion: We reported the first successful DMEK case for BK secondary to ALI. The use of a DMEK shooter for donor insertion and endoillumination assistance to visualize the DMEK graft was a useful technique for BK secondary to ALI. Keywords: argon laser iridotomy, bullous keratopathy, endoillumination, DMEK

Hideaki Yokogawa,1 Akira Kobayashi,1 Natsuko Yamazaki,1 Yoshiki Ueta,2 Yoshihiro Hashimoto,2 Naoko Tachi,2 Kazuhisa Sugiyama11Department of Ophthalmology, Kanazawa University Graduate School of Medical Science, Kanazawa, 2Department of Ophthalmology, Shinseikai Toyama Hospital, Imizu-shi, JapanBackground: The purpose of this paper is to report our experience of Descemet’s stripping and non-Descemet’s stripping automated endothelial keratoplasty (DSAEK/nDSAEK) for microcorneas using 6.0 mm donor grafts.Methods: Three eyes of two patients (a 56-year-old woman and a 59-year-old woman) with microcornea and suffering from bullous keratopathy were treated with either DSAEK or nDSAEK. A small donor graft (6.0 mm) was inserted into the anterior chamber using a double glide (Busin glide and intraocular lens sheet glide) donor insertion technique. Both patients were followed for at least 12 months. Clinical outcomes, including intraoperative and postoperative complications, visual acuity, and endothelial cell density were evaluated.Results: In all three cases (100%), no intraoperative complications were noted. In one case with a flat keratometry value (32.13 D), a partial donor detachment was noted one day postoperatively, but it was reattached by rebubbling. In another case, rejection was noted 8 months postoperatively, but treatment with systemic corticosteroids was successful. A clear cornea remained in all three cases (100%), with best-corrected visual acuity greater than 20/100 (mean 20/50) at 12 months. Mean postoperative endothelial cell counts were 2,603 ± 18 cells/mm2 at 6 months (7.4% decrease from preoperative donor cell counts) and 1,799 ± 556 cells/mm2 at 12 months (36.5% decrease).Conclusion: We report for the first time the successful use of a small donor graft (6.0 mm) for DSAEK/nDSAEK in cases of microcornea. Additional studies using a large number of patients are required to evaluate fully the potential advantages and drawbacks of small diameter donor grafts for microcornea.Keywords: microcornea, Descemet’s stripping, non-Descemet’s stripping, automated endothelial keratoplasty, small donor grafts

Noriaki Murata, Hideaki Yokogawa, Akira Kobayashi, Natsuko Yamazaki, Kazuhisa SugiyamaDepartment of Ophthalmology, Kanazawa University Graduate School of Medical Science, Kanazawa, JapanBackground: In this paper, we report our experience of the clinical features of single and repeated globe rupture after penetrating keratoplasty.Methods: We undertook a retrospective analysis of single and repeated globe ruptures following keratoplasty in eight eyes from seven consecutive patients referred to Kanazawa University Hospital over a 10-year period from January 2002 to March 2012. We analyzed their ophthalmic and demographic data, including age at time of globe rupture, incidence, time interval between keratoplasty and globe rupture, cause of rupture, complicated ocular damage, and visual outcome after surgical repair.Results: Five patients (71.4%) experienced a single globe rupture and two patients (28.6%) experienced repeated globe ruptures. Patient age at the time of globe rupture was 75.4 ± 6.8 (range 67–83) years. Four of the patients were men and three were women. During the 10-year study period, the incidence of globe rupture following penetrating keratoplasty was 2.8%. The time interval between penetrating keratoplasty and globe rupture was 101 ± 92 months (range 7 months to 23 years). The most common cause of globe rupture in older patients was a fall (n = 5, 79.8 ± 3.7 years, all older than 67 years). Final best-corrected visual acuity was .20/200 in three eyes (37.5%). In all except one eye, globe rupture involved the graft-host junction; in the remaining eye, the rupture occurred after disruption of the extracapsular cataract extraction wound by blunt trauma.Conclusion: Preventative measures should be taken to avoid single and repeated ocular trauma following penetrating keratoplasty.Keywords: repeated globe ruptures, penetrating keratoplasty, postoperative complications, ocular trauma

Natsuko Yamazaki,1 Akira Kobayashi,1 Hideaki Yokogawa,1 Yasuhisa Ishibashi,2 Yosaburo Oikawa,3 Masaharu Tokoro,4 Kazuhisa Sugiyama11Department of Ophthalmology, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan; 2Department of Ophthalmology, East Washinomiya Hospital, Kuki, Japan; 3Department of Medical Zoology, Kanazawa Medical University, Kahoku, Japan; 4Department of Parasitology, Kanazawa University Graduate School of Medical Science, Kanazawa, JapanPurpose: The purpose of the current study was to investigate ex vivo laser confocal microscopic findings of cultured Acanthamoeba trophozoites obtained from Acanthamoeba keratitis patients.Methods: Eight cultured samples of Acanthamoeba trophozoites from eight eyes of seven patients (mean age, 26.9 years; age range, 18–52 years) were used. Seven samples were from corneal scrapings of Acanthamoeba keratitis patients and one sample was from the solution in a soft contact lens case. Ex vivo laser confocal microscopy was performed to qualitatively evaluate the shape and degree of light reflection of the living Acanthamoeba trophozoites.Results: Ex vivo laser confocal microscopy demonstrated highly reflective, high-contrast Acanthamoeba trophozoites with no walls (mean size, 25.4 µm; range, 17.1–58.5 µm). The shapes of the trophozoites were highly pleomorphic, and some showed characteristic acanthopodia by laser confocal microscopy.Conclusion: Ex vivo laser confocal microscopy was effective in demonstrating cultured Acanthamoeba trophozoites of various shapes and sizes. The observations of the current study may be helpful when similar structures are identified under in vivo conditions.Keywords: Acanthamoeba, trophozoite, laser confocal microscopy

Hideaki Yokogawa,1 Akira Kobayashi,1 Natsuko Yamazaki,1 Yasuhisa Ishibashi,2 Yosaburo Oikawa,3 Masaharu Tokoro,4 Kazuhisa Sugiyama11Department of Ophthalmology, Kanazawa University Graduate School of Medical Science, Kanazawa, 2Department of Ophthalmology, East Washinomiya Hospital, Kuki, 3Department of Medical Zoology, Kanazawa Medical University, Kahoku, 4Department of Parasitology, Kanazawa University Graduate School of Medical Science, Kanazawa, JapanBackground: The purpose of this study was to report Acanthamoeba encystment in Bowman’s layer in Japanese cases of persistent Acanthamoeba keratitis (AK).Methods: Laser confocal microscopic images of the cornea were obtained in vivo from 18 consecutive eyes from 17 confirmed AK patients. Retrospectively, 14 cases treated over 4 months were categorized as a nonpersistent group and three cases that required prolonged therapy for more than 6 months were categorized as a persistent group. Clinical outcomes based on final best-corrected visual acuity were retrospectively analyzed, and selected confocal images were evaluated qualitatively for abnormal findings.Results: The final best-corrected visual acuity was significantly lower (P < 0.01) for patients in the persistent group compared with that in the nonpersistent group. At the initial visit, in vivo confocal microscopy demonstrated Acanthamoeba cysts exclusively in the epithelial layer in both the nonpersistent group (80%) and the persistent group (100%). At a subsequent follow-up visit, numerous Acanthamoeba cysts were observed in the epithelial cell layer and in Bowman’s layer in all patients with persistent AK, but Acanthamoeba cysts were undetectable in all cases with nonpersistent AK tested.Conclusion: Invasion of cysts into Bowman’s layer was characteristically observed in patients with persistence of AK. This finding suggests that invasion of Acanthamoeba cysts into Bowman’s layer may be a useful predictor for a persistent clinical course.Keywords: Acanthamoeba keratitis, Bowman’s layer, encystment

Akira Kobayashi, Hideaki Yokogawa, Kazuhisa SugiyamaDepartment of Ophthalmology, Kanazawa University Graduate School of Medical Science, Kanazawa, JapanBackground: The purpose of this study was to investigate pathological changes of the corneal cell layer in patients with map-dot-fingerprint (epithelial basement membrane) dystrophy by in vivo laser corneal confocal microscopy.Methods: Two patients were evaluated using a cornea-specific in vivo laser scanning confocal microscope (Heidelberg Retina Tomograph 2 Rostock Cornea Module, HRT 2-RCM). The affected corneal areas of both patients were examined. Image analysis was performed to identify corneal epithelial and stromal deposits correlated with this dystrophy.Results: Variously shaped (linear, multilaminar, curvilinear, ring-shape, geographic) highly reflective materials were observed in the “map” area, mainly in the basal epithelial cell layer. In “fingerprint” lesions, multiple linear and curvilinear hyporeflective lines were observed. Additionally, in the affected corneas, infiltration of possible Langerhans cells and other inflammatory cells was observed as highly reflective Langerhans cell-like or dot images. Finally, needle-shaped materials were observed in one patient.Conclusion: HRT 2-RCM laser confocal microscopy is capable of identifying corneal microstructural changes related to map-dot-fingerprint corneal dystrophy in vivo. The technique may be useful in elucidating the pathogenesis and natural course of map-dot-fingerprint corneal dystrophy and other similar basement membrane abnormalities.Keywords: cornea, confocal microscopy, map-dot-fingerprint dystrophy, epithelial basement membrane dystrophy, Heidelberg Retina Tomograph 2 Rostock Cornea Module (HRT 2-RCM)

Masayo Kimura, Akira Nishimura, Kazuhisa SugiyamaDepartment of Ophthalmology and Visual Science, Kanazawa University Graduate School of Medical Science, Kanazawa, JapanPurpose: To report a series of five cases of vitreous adhesions after blunt trauma caused by a baseball strike.Methods: The medical records of patients with ocular contusion after being struck by a baseball, who had undergone pars plana vitrectomy, were reviewed. An aqueous suspension of triamcinolone acetonide was used intraoperatively to facilitate visualization of the vitreous.Results: Five eyes were reviewed in this study. There were two cases of retinal detachment, two cases of traumatic macular hole, and one case of retinal detachment due to traumatic macular hole. Despite the surgical creation of posterior vitreous detachment, if not already present, the thin layer of localized vitreous adhesion to the retinal necrotic area with/without retinal hole was found between the major vascular arcades and the equator in all cases. The thin layer of the vitreous was removed with a vitreous cutter and diamond-dusted membrane scraper, but complete removal was impossible.Conclusions: A thin layer of localized vitreous adhesion at the area of retinal degeneration was observed in eyes following ocular contusion.Keywords: localized, vitreous adhesion, triamcinolone acetonide, ocular contusion, pars plana vitrectomy

Masayo Kimura,1 Akira Nishimura,1 Yoshiaki Saito,1 Hiroko Ikeda,2 Kazuhisa Sugiyama11Department of Ophthalmology and Visual Science, 2Department of Human Pathology, Kanazawa University Graduate School of Medical Science, Kanazawa, JapanPurpose: The purpose of the study was to report the outcomes for cases of proliferative vitreoretinopathy (PVR) that received retinotomy and removal of subretinal proliferative tissue under direct visualization using retinal turnover.Methods: Nineteen eyes with posterior and/or anterior grade C1–12 PVR that had undergone retinotomy and retinal turnover were reviewed. Main outcomes included the retinal reattachment rate, final best-corrected visual acuity (BCVA), postoperative intraocular pressure, extent of retinotomy, and complications.Results: Final retinal reattachment rates with silicone oil tamponade were 100%. The mean logarithm of the minimal angle of resolution (logMAR) BCVA was significantly improved (P = 0.001). Positive correlation was found between the extent of retinotomy and both preoperative logMAR BCVA (r = 0.663, P = 0.002) and postoperative logMAR BCVA (r = 0.619, P = 0.005). There was no correlation between the extent of retinotomy and the change in preoperative and postoperative logMAR BCVA (r = –0.267, P = 0.268). Negative correlation was found between preoperative logMAR BCVA and the change in logMAR BCVA (r = –0.587, P = 0.008). There was no correlation between the extent of retinotomy and the intraocular pressure at the final visit (r = –0.316, P = 0.188). Corneal decompensation due to silicone oil in the anterior chamber occurred in one eye.Conclusion: Removal of subretinal proliferative tissue with retinal turnover seems to be an effective procedure.Keywords: proliferative vitreoretinopathy, retinotomy, retinal turnover, subretinal proliferative tissue, under direct visualization

Akira Kobayashi, Hideaki Yokogawa, Kazuhisa SugiyamaDepartment of Ophthalmology, Kanazawa University Graduate School of Medical Science, Kanazawa, JapanAbstract: We describe a modified technique for loading donor corneal endothelial lamella onto a Busin glide® without causing wrinkles, as part of the procedure of Descemet-stripping automated endothelial keratoplasty. Briefly, after punching out a composite of the donor-endothelial lamella and a microkeratome-dissected cap, several drops of dispersive ophthalmic viscosurgical device are placed onto the endothelial surface. The Busin glide surface is then wetted with several drops of balanced salt solution. After the composite is transferred onto the Busin glide, hydrodissection of the potential space between the donor-endothelial lamella and the microkeratome-dissected cap is carefully performed to enable smooth detachment of these two lamellae. Whereas simply dragging the donor-endothelial lamella directly onto the glide can cause wrinkling or folding of the donor lamella, this technique enables smooth detachment of the composite without wrinkle or fold formation, and results in less endothelial cell damage.Keywords: DSAEK, Busin glide, endothelial keratoplasty

Tsugihisa Sasaki,1,2 Taeko Ota,3 Youko Ookura,4 Kazuhisa Sugiyama11Department of Ophthalmology, Kanazawa University School of Medicine, Kanazawa, Ishikawa; 2Department of Ophthalmology, Fukui Prefectural Hospital, Fukui; 3Department of Ophthalmology, Tonami General Hospital, Tonami-city, Toyama; 4Department of Ophthamology, Saiseikai Kanazawa Hospital, Kanazawa, Ishikawa, JapanBackground: The purpose of this work was to report on the performance of medial blepharosynechioplasty (MBSP), a newly devised technique for treating severe dry eye.Methods: In this retrospective, nonrandomized clinical trial, three cases with severe dry eye (Sjögren’s syndrome) associated with repeated punctal plug loss were treated using MBSP to create a synechia between the upper and lower lid medial borders of the puncta to suppress the lacrimal pump.Results: Postoperative follow-up showed improvement in the corneal condition in all three cases that persisted for 12–35 months. None of the patients had visual impairment.Conclusion: MBSP is a promising treatment for severe dry eye and merits further study.Keywords: dry eye, lacrimal pump suppression, medial blepharosynechioplasty

Kazuya Mori,&ast; Yunyan Ye,&ast; Hideaki Yokogawa, Tsubasa Nishino, Akira Kobayashi, Natsuko Mori, Yuko Takemoto, Kazuhisa Sugiyama Department of Ophthalmology, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan&ast;These authors contributed equally to this workCorrespondence: Hideaki Yokogawa, Department of Ophthalmology, Kanazawa University Graduate School of Medical Science, Takara-machi 13-1, Kanazawa, Ishikawa-ken, 920-8641, Japan, Tel +81-76-265-2403, Fax +81-76-222-9660, Email hyoko@med.kanazawa-u.ac.jpPurpose: The purpose of this study was to highlight the manifestations of glaucoma associated with cytomegalovirus (CMV) corneal endotheliitis.Methods: We reviewed the 34 patients that met the diagnostic criteria for CMV endotheliitis in our hospital, with special attention to the glaucoma status, including onset of glaucoma, glaucoma in the fellow eye, visual field defects, intraocular pressure, and final outcomes.Results: Thirty-four eyes of 34 patients (mean age, 69.1 ± 13.1 years; 31 males [91.2%]) with CMV corneal endotheliitis were enrolled. Thirty-two eyes (94.1%) had a history of a glaucoma diagnosis, which had been treated for 10.0 ± 10.1 years. Glaucoma in the fellow eye was noted in 16 cases (47.1%) and a history of Posner-Schlossman syndrome was noted in 13 cases (38.2%). Visual fields measured using a Humphrey field analyzer were normal-to-early stage (MD>-6dB) in 16 eyes (47.1%) and middle-to-late stage (MD≤-6dB) in 18 eyes (52.9%). The intraocular pressure decreased from 22.4 ± 10.6 mmHg at the initial visit to 14.9 ± 7.9 mmHg after medical treatment, including 0.5% topical ganciclovir (GCV) with and without a systemic anti-CMV agent, corticosteroid eye drops, and an anti-glaucoma agent (p< 0.01). During the follow-up period of 4.8 ± 3.0 years (range, 0.2– 10 years), 16 eyes (47.1%) required glaucoma surgery, including filtering surgery (7 eyes) and trabeculotomy only (9 eyes).Conclusion: Our case series showed that most of the patients with CMV corneal endotheliitis had glaucoma. Although medical therapy, including 0.5% topical GCV, had efficacy in lowering the intraocular pressure, one-half of the cases required glaucoma surgery. Therefore, ophthalmologists should strive to make an earlier diagnosis of CMV corneal endotheliitis by utilizing PCR testing of aqueous humor samples to prevent sight-threatening glaucomatous damage.Keywords: cytomegalovirus, corneal endotheliitis, secondary glaucoma, antiviral treatment